In vitro synthesis of RNA containing 5'-terminal structure 7nG(5')ppp(5')Apm... by purified wound tumor virus.
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Base Sequence↗
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[In memory of the death of Henrique Arouche de Toledo, president of APM, 5 May 1977].
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Brazil↗
The effect of systemic administration of dopamine and apomorphine on Plasma LH and prolactin concentrations in conscious rats.
The effect of systemic administration of various doses of dopamine (DA) and apomorphine (APM) on plasma gonadotropin and prolactin (Prl) concentrations in ovariectomized (OVX) as well as in ovariectomized, estrogen-progesterone (OEP)-primed rats bearing indwelling jugular venous catheters was evaluated. Intravenous (i.v.) infusion or pulse injection of 0.9% NaCl had no significant effect on plasma titers of LH or Prl. I.v. infusion of DA at 4 micrograms/kg-b.w./min induced a progressive increase in circulating LH concentration in OEP rats while infusion at a similar dose in OVX animals had no effect on plasma LH. I.v. injection of 100 micrograms DA or APM significantly increased LH at 15 min in OVX rats. Similarly, in OEP rats 100 micrograms of DA elevated plasma LH at 30 and 90 min while APM induced a significant elevation of plasma LH at 15 min after injection. In OVX rats injection of DA i.p. at a dose of 5 mg/kg-b.w. did not alter plasma LH levels, but a dose of 50 mg/kg-b.w. produced a significant reduction in plasma LH concentration. APM injected i.p. at either 5 or 50 mg/kg-b.w. doses was nearly equally effective in lowering plasma LH and the suppressive effect was significantly greater than with similar doses of DA. A single injection of LH-RH (100 ng in 0.2 ml of 0.9% NaCl) in animals pretreated 15 min earlier with an effective dose of APM (5 mg/kg-b.w.) produced a peak increase in LH titers 15 min after injection. The increment in plasma LH following LH-RH in APM-treated rats was comparable to that in rats which had received saline instead of APM. Prl levels were significantly lowered by each dose of DA and APM in OVX as well as in OEP rats. There was no significant change in plasma FSH titers induced by either drug in any of the experiments. It is concluded that DA may have different actions depending upon the dose and the endocrine state of the animal. Thus, i.v. infusion of low doses of DA in OEP animals or by pulse injection in both OVX and OEP rats can elevate plasma LH by activating the release of LH-RH from the hypothalamus, while large doses of DA in OVX animals may suppress the release of LH-RH.
Animals↗
The effect of apomorphine, amantadine and dimethylaminoadamantane on the level of cyclic AMP in the rat striatum.
The content of cyclic AMP (cAMP) in the slices of rat striatum and cerebral cortex was tested after incubation with various concentrations (10(-6)--10(4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), and dimethylaminoadamatane (DMAD), and incubation with DA, AMD and DMAD in combination with KCl (43 mM) or haloperidol (HP) (10(-5) M). APM, AMD, and DMAD act synergistically with DA, elevate the c-AMP content in the striatum less than DA dose and do not affect the level c-AMP in the slices of cerebral cortex. KCl potentiated the action of DA, but inhibited that of APM, AMD, and DMAD. HP was most effective in blocking the action of DA, and blocked more weakly the action of APM AMD, DMAD, and the action of DA, APM, AMD, and DMAD in the presence of high concentration of KCl. The results indicate that APM, AMD, and DMAD, are less specific stimulants of central dopaminergic structures than DA, and that the increase of c-AMP content in the slices of rat striatum caused by APM, AMD, and DMAD is due to depolarizing action of these compounds.
3',5'-Cyclic-AMP Phosphodiesterases↗
The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP.
We tested the effect of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) or haloperidol (HP) on the in vitro formation of c-AMP from ATP labelled intracellularly with exogenous 14C-adenine or from endogenous ATP in the slices of rat striatum. DA stimulated the synthesis of c-AMP from endogenous and 14C-adenine labelled ATP. Nonspecific stimulants of the dopaminergic system, APM, AMD and DMAD, stimulated the c-AMP synthesis much weaker than DA did. After application of APM, ADM or DMAD, the utilization of ATP formed from 14C/U/adenine for synthesis of c-AMP was lower than after DA. The effects of combined treatment with DA together with APM, AMD or DMAD was additive. HP, 1 X 10(-3) M did not change the amount of radioactive and total c-AMP, but inhibited the stimulatory action of DA and, to a lesser degree, of APM, AMD and DMAD. The synthesis of c-AMP from endogenous ATP stimulated with APM, AMD and DMAD in striate body slices was inhibited by HP more strongly than the synthesis of c-AMP from ATP labelled with exogenous 14C-adenine. The results indicate that ATP synthesized from intracellular adenyl nucleotides is more effectively utilized for the synthesis of c-AMP stimulated by APM, AMD or DMAD in striate body slices, than ATP labelled with 14C-adenine.
Adenine↗
Cancer Immune Responsiveness and MHC Class I Antigen Presentation: Mechanisms of Immune Escape and Immunotherapy Resistance in Gastrointestinal Cancers.
The Antigen Processing and Presentation Machinery (APM) is essential for immune surveillance by enabling the presentation of antigenic peptides to T lymphocytes and facilitating the elimination of infected or transformed cells. In cancer, the integrity of this process influences cancer immune responsiveness (CIR), defined as a tumour's capacity to be recognised by the immune system and respond to immunotherapy. Tumours with intact antigen presentation pathways are more likely to generate effective antitumour responses, whereas APM defects promote immune escape and therapeutic resistance. Cancer cells frequently evade immune detection through altered antigen processing or reduced expression of major histocompatibility complex (MHC) class I molecules, limiting tumour antigen presentation to cytotoxic T lymphocytes. These alterations are increasingly recognised as determinants of response to immune checkpoint inhibitors and potential predictive biomarkers. APM defects may be reversible or irreversible. Interferon-mediated signalling can restore MHC class I expression and T-cell cytotoxicity in some tumours, whereas permanent genomic alterations affecting human leukocyte antigen (HLA) class I genes, β2-microglobulin (β2-m), or interferon-γ (IFN-γ) pathway components can severely impair antigen presentation. Emerging evidence highlights four mechanistic levels of APM perturbation: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. Each contributes to distinct patterns of immune evasion. This review examines how MHC class I alterations influence CIR and contribute to immune evasion and immunotherapy resistance in gastrointestinal malignancies, while discussing therapeutic strategies to restore or bypass APM deficiencies.
Humans↗
The effect of agents stimulating dopaminergic system on incorporation of exogenous adenine into striate body slices of the rat.
We tested the effect of various concentrations (10(-6)--10(-4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) and haloperidol (HP) on in vitro incorporation of 14C/U/adenine to slices of the rat striate body. Two mechanisms participated in this incorporation: one of them (uptake I) of Km = 1.92 micron, the second (uptake II) of Km 434 micron, APM inhibited both uptake I and II, while AMD and DMAD only the uptake I. HP at concentration inhibiting the dopaminergic receptors did not affect the inhibition by APM, AMD or DMAD of incorporation of exogenous adenine to striatal slices. Incorporation of exogenous adenine was not related to stimulation by specific (DA) or unspecific (APM, AMD, DMAD) stimulants of dopaminergic receptors in the rat striate body. The inhibition of the uptake produced by APM, AMD and DMAD may be related to the mechanism of action of these compounds.
Adenine↗
Laparoscopic Surgery Is Associated With Reduced Small Bowel Obstruction Risk After Colorectal Cancer Surgery: A Nationwide Cohort Study of 5458 Patients.
INTRODUCTION: Postoperative small bowel obstruction (SBO) is a major complication following colorectal cancer surgery, yet evidence-based prevention strategies remain unclear. We aimed to clarify site-specific risk factors for SBO and evaluate the effectiveness of laparoscopic surgery and adhesion prevention materials (APMs) in preventing SBO after colorectal cancer surgery. METHODS: This retrospective cohort study analyzed 5458 patients who underwent colorectal cancer surgery at 32 Japanese institutions between 2012 and 2014. The primary endpoint was the 5-year risk of SBO. We evaluated the effects of laparoscopic surgery, APM use, and stoma creation on SBO risk. Clinical variables included demographics, tumor site, operative approach, operative details, and postoperative complications. Hospital-level clustering was addressed using mixed-effects logistic regression. RESULTS: Overall SBO incidence was 5.2% (n = 283). Rectal cancer had the highest risk, whereas all colonic sites except the descending colon showed significantly lower odds. Laparoscopic surgery was associated with a 42% reduction in odds (OR 0.58; 95% CI 0.45-0.74; p < 0.001), with significant reductions in ascending (NNT = 22.2, p = 0.001) and sigmoid colon surgery (NNT = 30.2, p = 0.003). APMs showed no protective effect (OR 1.01; 95% CI 0.78-1.32; p = 0.94). Stoma creation significantly increased SBO risk (OR 1.84; 95% CI 1.35-2.51; p < 0.001). Secondary analysis identified reoperation and postoperative ileus as additional independent risk factors. DISCUSSION: Laparoscopic surgery was associated with reduced long-term SBO risk, with significant benefits in ascending and sigmoid colon surgery. APMs showed no measurable benefit. Stoma creation increased SBO risk, with no observed difference between ileostomy and colostomy.
adhesion prevention material↗
Dynamic geometry of the left atrium and left ventricle in acute mitral regurgitation.
The instantaneous transverse diameter of the left atrium, left ventricular free wall segment length (SEG), and the long axis of the anterior papillary muscle (APM) length were measured throughout the cardiac cycle, using ultrasonic dimension gauges together with left atrial and left ventricular pressures in 12 open-chest dogs. During atrial contraction, left atrial diameter decreased from 19.7 to 18.7 mm, while left ventricular dimensions increased simultaneously. During ventricular ejection, percent shortening was 26% in SEG and 10% in APM, while atrial diameter increased continuously to 20.5 mm, with a concomitant rise in the v wave of left atrial pressure. After normal mitral valve opening, left atrial diameter decreased rapidly simultaneously with the y descent of atrial pressure. Graded mitral regurgitation was then produced by sectioning the chordae tendineae. With moderate mitral regurgitation, end-diastolic length of the SEG increased by 27%, while extent of shortening (delta L) was augmented by 96%. End-diastolic length of the APM increased by 7%, and delta L was augmented by 60%. Left atrial pressure was sharply elevated, with a distinct a wave followed by the more prominent v wave. End-diastolic diameter of the left atrium was enlarged to 22.9 mm with increased atrial shortening and expansion. As mitral regurgitation was increased to a severe degree by additional chordal rupture, end-diastolic length and delta L continued to increase both in SEG and APM. Left atrial pressure was further elevated (a wave 25 mm Hg and v wave 47 mm Hg). Left atrial end-diastolic diameter further increased in 24.9 mm. However, the amplitude of left atrial shortening and expansion decreased remarkably. In severe mitral regurgitation, isoproterenol and nitroprusside decreased left atrial pressure and diameter, restoring more forceful atrial shortening.
Acute Disease↗
Selective inhibition of tubulin synthesis by amiprophos methyl during flagellar regeneration in Chlamydomonas reinhardi.
Amiprophos methyl (APM) is a strong, readily reversible and highly selective inhibitor of tubulin synthesis in Chlamydomonas reinhardi. The extensive induction of tubulin synthesis that accompanies flagellar regeneration in this organism is prevented by 3 to 10 micrometerAPM. When applied after induction has begun, APM causes a rapid cessation of tubulin synthesis. Translation studies in vitro indicate that the lack of tubulin production in APM-treated cells is not due to a direct inhibition of tubulin messenger RNA translation but rather to a selective depletion of tubulin messenger RNA.
Chlamydomonas↗
Two methyltransferase activities in the purified virions of vesicular stomatitis virus.
In addition to an RNA-dependent RNA polymerase, purified vesicular stomatitis virus contains a methyltransferase activity which transfers the methyl group from the methyl donor, S-adenosyl-L-methionine, to two positions in the 5'-terminal capped structure of the nascent mRNA's synthesized in vitro as 7mG-(5)'ppp(5')Apm... In the present study it is shown that two distinct methyltransferase activities are discernible in the purified virus. The in vitro concentrations of the methyl donor specify the number and location of the methyl groups transferred to the capped 5'-termini of VSV mRNA's. Limited concentrations of the methyl donor result in a single methylation of the penultimate base in the 2'-hydroxyl position, that is, G(5')ppp(5')Apm..., whereas saturating concentrations of the methyl donor methylate the blocking guanosine residue at the 7-position, resulting in the dimethylated cap, 7mG(5')ppp(5')Apm... Pulse-chase experiments demonstrate that the monomethylated cap structure is the precursor substrate for the dimethylated cap. In this respect, vesicular stomatitis virus system is quite distinct from the vaccinia and reovirus systems. Virus purified from different host cells including hamster, mouse, and human contain both methyltransferase activities. The mRNA's containing monomethylated capped structures are poor templates for protein synthesis in vitro.
Kinetics↗
Structure, synthesis and orientation of microfibrils. V. On the recovery of Oocystis solitaria from microtubule inhibitor treatment.
Depending on the type of the inhibitor and its concentration one can experimentally induce two forms of aberrant microfibril orientations in O. solitaria cell walls through microtubule inhibitor application. The first form, designated "Intermediate", is characterized by the presence of cortical microtubules together with a spiral arrangement of microfibrils. The second form, designated "Parrallel", shows a wall with bundles of parallel oriented microfibrils without cortical microtubules. Taking colchicine as an example for a microtubule-inhibitor the "Parallel" form may be obtained with 10mM and the "Intermediate" with 5 to 1 mM solutions. Some microtubule-inhibitors such as methylbenzimidazole-2yl-carbamate (MBC) produce the "intermediate" form only. The recovery of normal microfibril orientation after inhibitor treatment is dependent on three factors: a) the developmental stage--young autospores just beginning to synthesize a wall are absolutely necessary; b) the application of inhibitors with the lowest effective concentration for c) the shortest possible time. Minimal concentrations for obtaining a "Full" effect range from 10 mM for colchicine to 1 micrometer for amiprophosmethyl (APM) with incubation periods from 3 to 9 hours. The return to the normal microfibril orientation has been achieved in all cases except after podophyllotoxin treatment. Since APM has been claimed to act selectively on tubulin synthesis in Chlamydomonas it was decided to compare the effects of this compound with cycloheximide (10 microgram/ml) on the recovery of microfibril orientation after colchicine treatment. In both cases no orientation recovery is possible although in the case of cycloheximide, synthesis of cellulose is drastically inhibited. This cycloheximide inhibition is fully reversible. During cycloheximide, but not APM, inhibition cortical microtubules return; however, due to the inhibition of cellulose synthesis itself, they cannot exert their orienting influence.
Chlorophyta↗
Aspartame--a sweet surprise.
The dipeptide ester L-aspartyl-L-phenylalanine methyl ester (APM) has been found to have a remarkably clean, sucrose-like taste with no off flavor and a potency 150-200 times sucrose. Subsequent work has shown that many alpha-amides of L-aspartic acid are sweet. Some results of stability studies and a taste panel evaluation of APM are reported.
Aspartame↗
Homologous and heterologous protection of mice with group A streptococcal M protein vaccines.
Purified streptococcal M proteins precipitated with alum (APM) were used to immunize mice. A trivalent vaccine of serotypes 1, 3, and 12 protected mice against challenges by homologous live streptococci and also conferred protection against serotypes 6 and 14 but not against a strain of group B streptococci. Monovalent APM vaccines afforded homologous protection and restricted heterologous protection. The extent of heterologous protection was a function of serotype combinations and was also dose dependent. Rabbit antisera exhibiting strong opsonic activities were active in vitro and in passive mouse protection only for homologous serotypes. Mouse antisera did not passively transfer protection and were not bactericidal in vitro. It was concluded that homologous and heterologous active mouse protection was most likely a result of shared antigenic determinants of the various M proteins although protection of mice could not be measured as a function of circulating anti-M antibodies.
Alum Compounds↗
Catecholaminergic regulation of TSH and growth hormone release in ovariectomized and ovariectomized, steroid-primed rats.
Third ventricular injection of dopamine (DA), Piribedil (ET-495), a DA receptor stimulator, norepinephrine (NE), epinephrine (E) and systemic administration of larger doses of DA and the receptor stimulant, apomorphine (APM), were used to evaluate their role in the regulation of TSH and GH secretion in ovariectomized (OVX) as well as ovariectomized, estrogen-progesterone treated (OEP) rats. Intraventricular or i.p. injection of DA or its agonists, ET-495, and APM, caused a lowering of plasma TSH and an elevation of plasma GH concentration in OVX as well as in OEP rats. In contrast, intraventricular injection of NE or E increased plasma TSH and GH concentration. On the basis of these results it is concluded that the central dopaminergic system is inhibitory to TSH secretion, as reflected in our exeriments by the significant reduction of TSH levels. On the other hand, the noradrenergic and adrenergic system has a stimulatory role on the release of TRH as evidenced by the increase in plasma TSH levels. Activation of dopaminergic, noradrenergic and adrenergic systems appears to promote release by hypothalamic GH releasing hormone as reflected in the enhanced concentration of plasma GH, but the precise physiological role of these biogenic amines in modulating the release of TSH and GH hormone remains to be elucidated.
Animals↗
On the individual pressure tolerance of the glaucomatous eye.
The individual pressure tolerance of any eye can be determined by taking account of the age, the values of the mean arterial pressure APm, the C/D ratio and the degree of deterioration of the visual field. The method developed opens the way to new possibilities in anti-glaucomatous therapy by making it possible to know the value of the maximum pressure (IPT) which can be supported by the eye under treatment. That treatment must succeed in reducing the value Pi to below the value IPT, if it is to be hoped that the evolution of the glaucoma will be stopped.
Blood Pressure↗
Effect of capping upon the mRNA properties of satellite tobacco necrosis virus ribonucleic acid.
The mRNA guanyltransferase-mRNA methyltransferases of vaccinia virions can be used to introduce a 5'-terminal m7g(5')pp(5')Apm... capping group onto the RNA of satellite tobacco necrosis virus (STNV RNA) to yield intact capped STNV RNA. Studies with an in vitro system from wheat germ and limiting quantities of capped and uncapped STNV RNA show that the rates and extents of formation of initiation complexes of protein synthesis by intact capped and uncapped STNV RNA are identical, suggesting that 5'-terminal cap groups cannot function in the translation of STNV RNA. Also, the cap analogue pm7G equally inhibits the initiation and the translation of limiting quantities of both capped and uncapped STNV RNA. These contrasting observations suggest that the wheat germ system contains a pm7G sensitive protein and that STNV RNA has a tertiary structure that restricts the function of an added 5'-terminal capping group. This theory is supported by observations that fragmented capped STNV RNA is better at forming initiation complexes than is equally fragmented uncapped STNV RNA.
Adenine Nucleotides↗
Association between smoking, tumor genetics, and outcomes in men with metastatic prostate cancer.
PURPOSE: Smoking has been associated with increased metastatic prostate cancer mortality, but the mechanisms behind this are largely unknown. We hypothesized that smoking increases the risk of genetic alterations associated with aggressive disease and/or the transformation to neuroendocrine prostate cancer (NEPC). PATIENTS AND METHODS: We utilized the Prostate Cancer Precision Medicine Multi-institutional Collaborative Effort (PROMISE) clinical genomic database for this retrospective analysis. We associated patient characteristics and tumor genetic data with smoking exposure at diagnosis (current, former, never and pack years) and with clinical outcomes, including overall survival (OS) from diagnosis or time to developing metastatic disease and NEPC status. RESULTS: We identified 2353 men with prostate cancer and next generation somatic tumor sequencing evaluable for analysis in PROMISE, including 8% current, 39% former, and 52% never smokers. Current smokers were more likely to be younger and to have metastatic (M1 or N1) disease at diagnosis, and less likely to have prior local therapy (all p < 0.001). Current smoking was associated with worse OS from diagnosis (99.9 mo vs 137.6 mo, HR 1.42, 95% CI 1.14-1.77), which remained significant after adjusting for disease characteristics. We found no difference in the percentage of NEPC at initial diagnosis or at any time between current, former, and never smokers (p = 0.8). We found positive associations between smoking status and genetic alterations in SPOP (current: 15%, former 6.7%, never 3.8%; p = 0.018), FGFR1 (current 10%, former 0.4%, never 1.1% p = 0.001), and ARID1A (current 5.1%, former 2.2%, never 0.4%; p = 0.035) in patients with metastatic androgen pathway modulator sensitive prostate cancer (APMS). CONCLUSION: Active smoking is associated with worse overall and prostate cancer specific survival as compared to never/former smoking and was associated with specific tumor genetic alterations but not small cell/NEPC transformation.
Journal Article↗